The human secretome and kidney fibrosis – identification of novel fibroblast biology through exploitation of the human secretomics library.

Diabetic nephropathy is the world’s leading and most rapidly growing cause of end stage renal disease, with up to 40 % of all diabetic patients developing chronic kidney damage – a common manifestation of which is tubulointerstitial fibrosis, driven by overactive fibroblast cells. The human secretomics project is a collaboration between KTH and AstraZeneca to develop methods to purify from cell factories all 6400 human membrane and secreted proteins. The resultant library of highly bioactive molecules will enable exploration of novel biology and identification of tractable protein targets for drug discovery. We have for the first time used a 700 set secretomics library as a novel modality to probe the biology of the causative cell type in chronic kidney disease, fibroblasts. By building a high content imaging assay to follow the phenotypic fate of primary human kidney fibroblasts we have screened the secretomics library alongside a standard small molecule campaign. This innovative use of the human secretome library enabled us to identify novel regulators of fibroblast biology not previously identified, and whose identification will now enable strategies to develop next generation biological treatments that will halt or slowdown disease progression in patients with chronic kidney disease.